Benzyl-oxyalkyl aromatic



Patented Sept. 12, 1939 BENZYL- O-XYALKYL AROMATIG 'SULPHONATE S Courtland L. Butler and Leonard H. Cretcher, Pittsburgh, Pa., assignors to Mellon Institute of lndustrial Research, a corporation of Pennsylvania No Drawing. Application April 26, 1937, Serial N0. 138,936

5 Claims.

This invention consists in a new group of compositions, the benzyl-oxyalkyl aromatic sulphonates. These substances are valuable reagents in the synthesis of useful organic compounds and medicinal's of various types. They may conveniently be used for the introduction of the benzyl-oxy-alkyl and the hydroxyalkyl group into hydroxy, amino, and hydroxy-amino substances, and into medicinal substances, such as alkaloids.

The benzyl-oxyalkyl aromatic sulphates may, we have discovered, readily be prepared by causing reaction to take place between the monobenzyl ethers of various glycols and aromatic sulphonyl chlorides, in the presence of an alkaline condensing agent, such as pyridine. The crystalline or liquid products of reaction are isolated and purified by usual methods, available to the organic chemist.

EXAMPLE l.Prepamtion of benzyl-oznyethyl benzene sulphonate To a cold mixture of 78 parts of ethylene glycol monobenzyl ether and 40 parts of pyridine is slowly added with stirring a mixture of 88 parts of benzene sulphonyl chloride and 30 parts of pyridine. After standing several hours in the cold, the reaction product, benzyl-oxyethyl benzene sulphonate, is worked up according to usual methods. The substance is isolated as a high boiling liquid.

EXAMPLE 2.-Preparation of benzyZ-oxyethyl ptoluene sulphonate To a cold mixture of 31 parts of ethylene glycol monobenzyl ether and 30 parts of pyridine is slowly added with stirring 38 parts of p-toluene sulphonyl chloride. The mixture is then allowed to stand several hours. On slow dilution with water, crystalline benzyl-oxyethyl toluene sulphonate separates from the diluted pyridine. It is filtered, washed, dried, and recrystallised, if desired.

EXAMPLE 3.Preparation of -benzyl omypropyl p-toluene sulphonate In a similar way a mixture of 83 parts of trimethylene glycol monobenzyl ether and 80 parts of pyridine is treated with parts of p-toluene sulphonyl chloride. The crystalline product is worked up in the usual way.

EXAMPLE 4.Prepamtion of 1-benzyloa2y Z-propyl p-toluene sulphonate (ix-methyl -benzylozryethyl p-toluene sulphone') A mixture of 83 parts of propylene glycol 1- monobenzyl ether and 80 parts of pyridine is simin which R=radical of ROI-I, the hydroxy compound alkylated with a benzyl oxalkyl aromatic sulphonate.

EXAMPLE 1.Preparatz'on of beneyZ-oasyethyl phenyl ether 47 parts of phenyl and 33 parts of 85% KOI-I are dissolved in alcohol. 153 parts of benzyloxyethyl p-toluene sulphonate are added. The mixture is heated on a water bath for 2 hours and the reaction product, a high boiling, wateri-nsoluble liquid is isolated in the usual way.

EXAMPLE 2.Pre: aration of beneyZ-omyethyl (pdz'benzyl oxyethyl-aminophenyl) ether and phenyl morpholine p-hydroxyethyl ether p-Aminophenol is similarly digested in alkaline alcoholic solution with benzyl-oxyethyl p-toluene sulphonate. The benZyl-oxyethyl (p-dibenzyl-oxyethyl aminophenyl) ether is worked 35 up by the usual methods. 'It may be converted to a crystalline neutral sulphonate if desired.

Phenyl morpholine p-hydroxyethyl ether is prepared from benzyl-oxyethyl (p-dibenzyl-oxyethyl aminophenyl) ether by converting the latter into 0 hydrochloride salt and hydrolyzing in dilute hydrochlori'c acid. It yields a crystalline acetate on I treatment with acetyl chloride.

EXAMPLE 3.Preparation of b-enzyl-oxyethyl 8- quinolyl ether 58 parts of 8-hydroxy'quinoline are converted to potassium salt in alcoholic solution and digested with 122.4 parts of benzyl-oxyethyl p-toluene sulphonate for two hours on a Water bath. The product, benzyl-oxyethyl B-quinolyl ether is separated in the usual way.

EXAMPLE 4.-Prep'aration of hydrozryethyl 8-quinolyl ether parts of benzyl-oxyethyl 8-quinolyl ether are dissolved in 500 parts of dilute hydrochloric acid containing 130 parts of concentrated acid. On distilling the benzyl group is hydrolyzed off as benzyl chloride which is carried over in the distillate. The resulting hydroxyethyl S-quinolyl ether is worked up according to the usual methods.

Hydroxyethyl 8-quinolyl ether yields a crystal; line hydrochloride with one equivalent of HCl.

EXAMPLE 5.Preparation of benzyl-omyethyl apocupreine using benzyl-oryethyl-benzene' sul phonate 30 parts of apocupreine are convertedto' potassium salt in alcoholic solution, and digested for two hours on a water bath with 26 parts of benzyl-oXyethyl-benzene sulphonate. The reaction product, benzyl-oxyethyl apocupreine, is worked up in the usual way. The substance may be conveniently recrystallized from acetone, if desired.

EXAMPLE 6.Preparation of benzyZ-omyethyl apocupreine using benzyl-oxyethyl p-toluene sulphonate In a similar way 50 parts of apocupreine in the form of its potassium salt in alcoholic solution are treated With 48 parts of benzyl-oxyethyl p-toluene sulphonate, and the product, benzyl-oxyethyl apocupreine, is worked up by the usual method.

EXAMPLE '7.- Prepamtion of benzyZ-oznyethyl apocupreine from B-chloroeth'yl apocupreine B-chloroethyl apocupreine is prepared in the usual way by alkylating the potassium salt of apocupreine with B-chloroethyl p-toluene sulphonate.

90 parts of B-chloroethyl apocupreine are digested with benzyl alcohol in which is dissolved 6.5 parts of sodium. The reaction mixture is diluted with ether, and the solution filtered from sodium chloride. The desired product, benzyloxyethyl apocupreine, is extracted from the ether solution with dilute sulphuric acid and worked up in the usual way.

EXAMPLE 8.Prepamtion of benzyZ- omyethyl hydrocupreine 90 parts of hydrocupreine are converted to potassium salt in alcoholic solution and warmed for two hours with 88 parts of benzyl-oxyethyl p-toluene sulphonate. The desired product, benzyl-oxyethyl hydrocupreine, is worked up according to the usual methods.

" EXAMPLE 9.Preparation of I-benzyloa:ypropyl apocupreine 46 parts of apocupreine in the form of potassium salt in alcoholic solution are similarly treated with 48 parts of I-benzyloxypropyl p-toluene sulphonate. The desired product, Ibenzyloxypropyl apocupreine, is worked up in the usual Way.

EXAMPLE 10.Preparation of betzzylomy-Z-propyl apocupreine (or-methyl ,B-benzylomyethyl apocup'reine) 62 parts of apocupreine in the form of potassium salt in alcoholic solution are similarly treated with 64 parts of l-benzyloxy-Z-propyl p-toluene sulphonate (oz-methyl fi-benzyloxyethyl ptoluene sulphonate). The l-benzyloxy 2-propyl apocupreine (oz-methyl p-benzyloxyethyl apocu priene is worked up in the customary manner.

EXAMPLE 11.Prepa,ration of hydroryethyl apocuprez'ne from benzyZ-occyethyl apocupreine 9 parts of benzyl-oxyethyl apocupreine are dissolved in 60 parts of dilute hydrochloric acid containing 16 parts of concentrated hydrochloric acid. On distillation the benzyl group is hydrolyzed off as benzyl chloride which is carried over in the distillate. The last of the benzyl chloride is removed by steam distillation. Hydroxyethyl apocupreine remains in the acid solution in the reaction vessel. It is worked up by the usual procedures.

EXAMPLE 12.Preparation of hydroxyethyl hydrocupreine from benzyZ-oxyethyl hydrocuprez'ne In a similar way benzyl-oxyethyl hydrocupreine is hydrolyzed in dilute hydrochloric acid to hydroxyethyl hydrocupreine and the product is worked up in the ordinary way.

EXAMPLE l3.--Preparation of F-hydroztypropyl apocupreine from benzyloasyprropyl apocupreine In a similar way 1-benzyl oxypropyl apocupreine is hydrolyzed in dilute hydrochloric acid to Ihydroxypropyl apocupreine and the product worked up as usual.

where OR is an oxyalkyl group selected from oxyethyl and oxypropyl and R is an aryl radical of the benzene series.

2. As a new composition of matter, benzyl-oxyethyl benzene sulphonate,

CcHsSOaCHzCI-IzOCHzCsI-R 3. As a new composition of matter, benzyl oxyethyl p-toluene sulphonate,

4. As a new composition of matter, I-ben zyloxypropyl p-toluene sulphonate,

C'7H7SO3CH2CH2CH2OCH2C6H5 5. As a new composition of matter, l-benzyloxy 2-propyl p-toluene sulphonate (at-methyl [ii-benzyloxyethyl p-toluene sulphonate),

C'7H7SO3CH(CH3) CHzOCHzCsHs COURTLAND L. BUTLER. LEONARD H. CRETCI-IER. 

